# Role of Intestinal Microbiota in Dyslipidemia and Atherosclerosis Induced by Ambient Ultrafine Particles

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $505,331

## Abstract

ABSTRACT
Cumulative epidemiological and experimental data have shown that exposure to ambient particulate matter
(PM) leads to increased cardiovascular morbidity and mortality. A causal association between PM exposure
and atherosclerosis has been established. Unfortunately, the pathogenic mechanisms remain unknown
preventing the development of effective therapeutic strategies. We have found that exposures to ultrafine
particles (UFP, PM with an aerodynamic diameter < 0.2 µm) and diesel exhaust lead to increased lipid
peroxidation in the lungs and systemic tissues, accompanied by dyslipidemia and a proatherogenic plasma
lipoprotein profile, consisting of LDL particles more susceptible to oxidation and dysfunctional HDL particles
with loss of their vascular protective properties. However, the mechanisms by which inhalation of UFP lead to
effects in the systemic vasculature remain unknown. We and others have shown that exposure to PM lead to
marked changes in the gut microbiome, which is known to modulate host metabolism, immunity, and
inflammatory responses resulting in pathological conditions, including cardiovascular diseases. This project will
evaluate whether a novel microbome-mediated gastrointestinal (GI) pathway mediates PM-induced
dyslipidemia and atherosclerosis. Our preliminary data indicate that oral administration of UFP or inhaled
diesel exhaust induces changes in gut microbiota diversity, which associates with lipid oxidation in the
intestines and blood, dyslipidemia, and liver steatosis together with decreased expression of hepatic PPARα,
which may mediate some of the UFP-mediated cardiometabolic actions. Our central hypothesis is that
inhalation exposure to ambient UFP induces dyslipidemia and atherosclerosis partly due to changes in gut
microbiota composition that lead to dysregulation of PPARα in the liver. We will test this hypothesis via three
specific aims: 1) To determine the changes in gut microbiota composition following pulmonary exposure to
ultrafine PM. We will perform both UFP inhalation and oral gavage studies to characterize the relative changes
in microbiota in Ldlr KO and C57BL/6 mice. 2) To examine whether UFP-induced dyslipidemia and
atherosclerosis are mediated by the gut microbiome. The microbiota of UFP-exposed mice will be transferred
into germ-free and antibiotic-treated Ldlr KO and C57BL/6 recipients to establish a causal link between UFP-
induced gut microbiota effects, lipid metabolism, and atherosclerosis. 3) To determine whether UFP-mediated
changes in gut microbiota promote lipid metabolic effects and atherosclerosis via modulation of PPARα
expression in the liver. We will determine if UFP-induced changes in hepatic PPARα mediate effects induced
by UFP exposure on lipid and atherosclerosis using PPARα KO mice. The results are expected to enhance our
understanding of a novel gut microbiome-mediated pathway by which UFP induce adverse systemic effects. If
successful, results derived from this project are e...

## Key facts

- **NIH application ID:** 10005422
- **Project number:** 5R01ES029395-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jesus Antonio Araujo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $505,331
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005422

## Citation

> US National Institutes of Health, RePORTER application 10005422, Role of Intestinal Microbiota in Dyslipidemia and Atherosclerosis Induced by Ambient Ultrafine Particles (5R01ES029395-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10005422. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*